Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in
ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic
Stem Cells

J 2017

Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

KUČERA, Jan, Julie NETUŠILOVÁ, Stanislava SLADEČEK, Martina KOHUTKOVÁ LÁNOVÁ, Ondřej VAŠÍČEK et. al.

Základní údaje

Originální název

Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

Autoři

KUČERA, Jan (203 Česká republika, domácí), Julie NETUŠILOVÁ (203 Česká republika, domácí), Stanislava SLADEČEK (688 Srbsko, domácí), Martina KOHUTKOVÁ LÁNOVÁ (203 Česká republika, domácí), Ondřej VAŠÍČEK (203 Česká republika), Kateřina ŠTEFKOVÁ (203 Česká republika, domácí), J. NAVRÁTILOVÁ (203 Česká republika), Lukáš KUBALA (203 Česká republika) a Jiří PACHERNÍK (203 Česká republika, garant, domácí)

Vydání

Oxidative Medicine and Cellular Longevity, London, HINDAWI LTD, 2017, 1942-0900

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.936

Kód RIV

RIV/00216224:14310/17:00100432

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1155/2017/4386947

UT WoS

000406334700001

Klíčová slova anglicky

PROTEIN PHOSPHATASE 2A; CHLORIDE-INDUCED APOPTOSIS; INDUCIBLE FACTOR 1-ALPHA; MAP KINASE; SELF-RENEWAL; HIF-1-ALPHA ACCUMULATION; UNDIFFERENTIATED STATE; TYROSINE-PHOSPHATASE; REDOX-REGULATION; IRON CHELATOR

Štítky

NZ, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 4. 2018 09:52, Ing. Nicole Zrilić

Anotace

V originále

Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1 alpha-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O-2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP) 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A) regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS) level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1.

Citovat

KUČERA, Jan, Julie NETUŠILOVÁ, Stanislava SLADEČEK, Martina KOHUTKOVÁ LÁNOVÁ, Ondřej VAŠÍČEK, Kateřina ŠTEFKOVÁ, J. NAVRÁTILOVÁ, Lukáš KUBALA a Jiří PACHERNÍK. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. Oxidative Medicine and Cellular Longevity. London: HINDAWI LTD, 2017, roč. 2017, July, s. 1-16. ISSN 1942-0900. Dostupné z: https://dx.doi.org/10.1155/2017/4386947.

@article{1411875,
   author = {Kučera, Jan and Netušilová, Julie and Sladeček, Stanislava and Kohutková Lánová, Martina and Vašíček, Ondřej and Štefková, Kateřina and Navrátilová, J. and Kubala, Lukáš and Pacherník, Jiří},
   article_location = {London},
   article_number = {July},
   doi = {http://dx.doi.org/10.1155/2017/4386947},
   keywords = {PROTEIN PHOSPHATASE 2A; CHLORIDE-INDUCED APOPTOSIS; INDUCIBLE FACTOR 1-ALPHA; MAP KINASE; SELF-RENEWAL; HIF-1-ALPHA ACCUMULATION; UNDIFFERENTIATED STATE; TYROSINE-PHOSPHATASE; REDOX-REGULATION; IRON CHELATOR},
   language = {eng},
   issn = {1942-0900},
   journal = {Oxidative Medicine and Cellular Longevity},
   title = {Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells},
   volume = {2017},
   year = {2017}
}

TY  - JOUR
ID  - 1411875
AU  - Kučera, Jan - Netušilová, Julie - Sladeček, Stanislava - Kohutková Lánová, Martina - Vašíček, Ondřej - Štefková, Kateřina - Navrátilová, J. - Kubala, Lukáš - Pacherník, Jiří
PY  - 2017
TI  - Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells
JF  - Oxidative Medicine and Cellular Longevity
VL  - 2017
IS  - July
SP  - 1-16
EP  - 1-16
PB  - HINDAWI LTD
SN  - 19420900
KW  - PROTEIN PHOSPHATASE 2A
KW  - CHLORIDE-INDUCED APOPTOSIS
KW  - INDUCIBLE FACTOR 1-ALPHA
KW  - MAP KINASE
KW  - SELF-RENEWAL
KW  - HIF-1-ALPHA ACCUMULATION
KW  - UNDIFFERENTIATED STATE
KW  - TYROSINE-PHOSPHATASE
KW  - REDOX-REGULATION
KW  - IRON CHELATOR
N2  - Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1 alpha-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O-2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP) 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A) regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS) level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1.
ER  -

KUČERA, Jan, Julie NETUŠILOVÁ, Stanislava SLADEČEK, Martina KOHUTKOVÁ LÁNOVÁ, Ondřej VAŠÍČEK, Kateřina ŠTEFKOVÁ, J. NAVRÁTILOVÁ, Lukáš KUBALA a Jiří PACHERNÍK. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells. \textit{Oxidative Medicine and Cellular Longevity}. London: HINDAWI LTD, 2017, roč.~2017, July, s.~1-16. ISSN~1942-0900. Dostupné z: https://dx.doi.org/10.1155/2017/4386947.

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